Changes in Treatment of Neuroendocrine Tumors Highlight Oncology News
Top news of the week in cancer drug development.
Top news of the week in cancer drug development.
Inotuzumab Ozogamicin Granted Breakthrough Status for ALL
The FDA granted the anti-CD22 antibody-drug conjugate inotuzumab ozogamicin a breakthrough therapy designation as a potential treatment for patients with relapsed or refractory acute lymphoblastic leukemia.
In the open-label phase III trial, which was the basis for the designation, inotuzumab ozogamicin demonstrated a complete response or CR with incomplete platelet recovery rate of 80.7% compared with 33.3% for chemotherapy in patients with relapsed or refractory ALL (P <.0001). In those who achieved a CR/CRi, 78.4% were minimal residual disease-negative (<0.01% cells by central flow cytometry).
The duration of first complete remission was ≥12 months in 43% of patients treated with inotuzumab ozogamicin compared with 35% in the chemotherapy arm. Overall survival data were not yet mature at the time of the analysis.
Based on the initial assessment of the trial, Pfizer, the company developing the drug, has entered into discussions with the FDA and other regulatory authorities. The breakthrough designation was designed to help expedite this regulatory process.
FDA Approves HIFU for Prostate Cancer
The FDA has issued a de novo clearance for a minimally invasive high-intensity focused ultrasound device called Sonablate 450 for prostate tissue ablation. The device is intended for patients with low- to high-risk prostate cancer with a PSA lower than 10 ng/mL who have progressed on external beam radiation therapy.
The positive decision for Sonablate 450 was preceded by a negative vote from the FDA's Gastroenterology and Urology Devices Panel in October 2014. At this hearing, the panel expressed desires to review further data on the HIFU device.
In data from the first 100 patients in a 200 patients trial, 50% of those treated with Sonablate 450 obtained local control of their disease, which was defined as a PSA nadir of 0.5 ng/mL or lower along with a negative biopsy at 12 months (97.06% CI, 0.39-0.61; P = .0206).
In those with biopsy results at 12 months (n = 78), the local control rate jumped to 64.1% (97.06% CI, 0.52-076; P = .0001). The FDA’s decision marks the first approved device to use HIFU technology in the United States, despite its approval in 49 other countries around the world.
2015 NANETS Symposium
During the 2015 NANETS Symposium, three sequential presentations covered the most practice changing findings for patients with neuroendocrine tumors. In the first, robust clinical activity was seen for everolimus in patients with lung/GI NETs, offering a much-needed option for patients with these tumors.
In the phase III RADIANT-4 trial, everolimus improved progression-free survival by 7.1 months compared with placebo, representing a 52% reduction in the risk of progression or death. Given past experience with the medication, those at the conference indicated that everolimus would quickly become the standard of care following FDA approval
In another study, the radiopharmaceutical Lu-Dotatate demonstrated an unprecedented 79% reduction in the risk of progression or death compared with high-dose octreotide LAR in patients with progressive, metastatic midgut neuroendocrine tumors. Median PFS had not been reached for Lu-Dotatate compared with 8.4 months for octreotide
In the third study, telotristat etiprate, a novel serotonin synthesis inhibitor, helped reduce daily bowel movements for patients with carcinoid syndrome no longer responding to standard-of-care therapies.
In the phase III TELESTAR study, telotristat etiprate decreased mean daily bowel movements by 35% among participants who received 500 mg of the drug three times a day and 29% among those who took 250 mg three times a day, compared with 17% for individuals who received a placebo
The FDA will review findings from all three studies.
NCCN Incorporates Costs Into Guidelines
NCCN announced a new series of cancer regimen guidelines that incorporate cost considerations to aid and facilitate broader discussion between physicians and patients about treatment. The guidelines, labeled Evidence Blocks, combine efficacy, safety, quality of evidence, consistency of evidence, and affordability.
These variables are represented in a matrix block that awards each a score from 1 to 5, with a score of 1 being the lowest. The first two sets of evidence blocks were released for chronic myeloid leukemia and multiple myeloma.
Affordability of the regimens in the guideline is based on a spectrum of cost considerations that include the overall treatment cost, toxicity, and other elements of care—not just the cost of a particular drug.
Variability of costs between institutions and also individual differences in patient condition and choices in care complicate the search for exact costs; however, there was very strong consistency in consensus estimates among panelists who contributed to the matrix rankings.
Separate Evidence Blocks are expected by the end of 2017 for all 61 of the NCCN guidelines.
Aprepitant Reduces Cough Associated With Lung Cancer
Treatment with aprepitant was shown to significantly reduce cough in patients with lung cancer, according to findings of the first antitussive trial in patients with lung cancer using objective quantification of cough.
This exploratory, single-arm, double-blind, randomized, placebo-controlled, crossover trial enrolled 20 patients (mean age = 66) who had lung cancer and reported bothersome cough. At baseline after 24 hours of monitoring, daytime cough frequency per hour in 19 patients was 15.9 (95% CI, 10.1-28.3).
When patients were given aprepitant (n = 18), cough frequency was 12.8 (95% CI 8.7-18.8). When 19 patients received placebo capsules, cough frequency was higher at 16.2 (11.3-23.0; overall P = .03).
Subjective ratings of cough using the Manchester Cough in Lung Cancer Scale were 25.2 at baseline followed by 19.5 and 21.7 for those receiving aprepitant and placebo, respectively (P <.001).
Overall, adverse events were minimal, and aprepitant was well-tolerated.